The aims of the Neuropathology Core are to provide technical resources, laboratory facilities and professional expertise for the collection, diagnosis and storage of tissue obtained at autopsy from patients with dementia and control subjects studied in the Clinical Core, National Cell Repository Core, and from referral cases from other institutions. The Neuropathology Core will provide information about pathologic data to referring physicians and families, as well as well-characterized tissue to basic researchers. In addition, the Core will be involved in continuing education to physicians, researchers, technicians and the community about new developments emerging from Alzheimer s disease (AD) research. Our understanding of the clinical, pathologic and molecular aspects of AD and other dementias has advanced rapidly during the last ten years. Brain tissue of demented individuals must be studied for diagnostic and research purposes using a multidisciplinary approach. We have expanded our Dementia Laboratory for degenerative brain diseases and our tissue repository. The Core has contributed to the investigations of hereditary presenile dementias by: (i) characterizing familial AD with mutations in the APP and PSI genes, (ii) characterizing the neuropathologic phenotypes of sporadic and hereditary prion diseases, (iii) characterizing the neuropathologic phenotypes of frontotemporal dementia with parkinsonism linked to chromosome 17, and (iv) discovering novel mutations in APP, PSI, PRNP, Tau, and Neuroserpin, as well as unclassified forms of presenile dementia. We are expanding our mission, integrating molecular technology to assist in the neuropathologic diagnosis of dementia. By using brain tissue obtained at autopsy, we define the molecular genetics of individual cases. We are combining data obtained by neurohistology, immunohistochemistry and immunocytochemistry to recognize and characterize the localization and the antigenic profile of molecules that are important to the pathogenesis of dementia. These studies, carried out in parallel with molecular analysis, are fundamental to understanding disease etiology and phenotypic heterogeneity. We consider this multidisciplinary approach to be the hallmark of the IADC Neuropathology Core, and it will aid us in providing a definitive diagnosis of dementing disorders.